TSH-CHECK-1 test: diagnostic accuracy and potential application to initiating treatment for hypothyroidism in patients on anti-tuberculosis drugs.

Thyroid-stimulating hormone (TSH) promotes expression of thyroid hormones which are essential for metabolism, growth, and development. Second-line drugs to treat tuberculosis (TB) can cause hypothyroidism by suppressing thyroid hormone synthesis. Therefore, TSH levels are routinely measured in TB patients receiving second-line drugs, and thyroxin treatment is initiated where indicated. However, standard TSH tests are technically demanding for many low-resource settings where TB is prevalent; a simple and inexpensive test is urgently needed

Second line therapy in malignant pleural mesothelioma: a systematic review

After the implementation of standard first line chemotherapy with platinum and antifolates in pleural mesothelioma, patients are confronted with a need for second line treatment at relapse or progression. We conducted a systematic review of the literature for the activity, effectiveness and toxicity of second line treatment. The results are presented according to the class of drugs: chemotherapy and targeted or biological agent. (C) 2015 Elsevier Ireland Ltd. All rights reserved.Pulmonolog

Availability and affordability of treatment for Human African Trypanosomiasis.

Human African Trypanosomiasis (HAT) is a re-emerging disease whose usual treatments are becoming less efficient because of the increasing parasite resistance. Availability of HAT drugs is poor and their production in danger because of technical, ecological and economic constraints. In view of this dramatic situation, a network involving experts from NGOs, WHO and pharmaceutical producers was commissioned with updating estimates of need for each HAT drug for the coming years; negotiations with potential producers of new drugs such as eflornithine; securing sustainable manufacturing of existing drugs; clinical research into new combinations of these drugs for first and second-line treatments; centralizing drug purchases and their distribution through a unique non-profit entity; and addressing regulatory and legal issues concerning new drugs

Molecular Characterization of the Resistance of Mycobacterium tuberculosis to Second Line Drugs in Côte d’Ivoire

Purpose: To characterize the resistance of Mycobacterium tuberculosis to second line drugs using a line probe assay.Methods: Multi-drug resistant strains of Mycobacterium tuberculosis isolated between December 2008 and December 2009 were tested for resistance to fluoroquinolones and second-line injectable drugs using GenoType® MTBDRsl.Results: Thirty eight strains gave interpretable results. None of them had a mutation in the gyrA gene. Regarding second-line injectable drugs, 4 strains (11 %) were resistant to aminoglycosides/ capreomycin and all of them harbored A1401G mutation.Conclusion: No extensive drug resistant strains were observed. A relatively high proportion of strains were resistant to at least one second-line injectable drug. Resistance mechanism seemed similar for all of them.Keywords: Mycobacterium tuberculosis, Line probe assay, GenoType® MTBDRsl, Aminoglycosides Capreomycin, Mutatio

Cost-Effectiveness of Treating Multidrug-Resistant Tuberculosis

BACKGROUND: Despite the existence of effective drug treatments, tuberculosis (TB) causes 2 million deaths annually worldwide. Effective treatment is complicated by multidrug-resistant TB (MDR TB) strains that respond only to second-line drugs. We projected the health benefits and cost-effectiveness of using drug susceptibility testing and second-line drugs in a lower-middle-income setting with high levels of MDR TB. METHODS AND FINDINGS: We developed a dynamic state-transition model of TB. In a base case analysis, the model was calibrated to approximate the TB epidemic in Peru, a setting with a smear-positive TB incidence of 120 per 100,000 and 4.5% MDR TB among prevalent cases. Secondary analyses considered other settings. The following strategies were evaluated: first-line drugs administered under directly observed therapy (DOTS), locally standardized second-line drugs for previously treated cases (STR1), locally standardized second-line drugs for previously treated cases with test-confirmed MDR TB (STR2), comprehensive drug susceptibility testing and individualized treatment for previously treated cases (ITR1), and comprehensive drug susceptibility testing and individualized treatment for all cases (ITR2). Outcomes were costs per TB death averted and costs per quality-adjusted life year (QALY) gained. We found that strategies incorporating the use of second-line drug regimens following first-line treatment failure were highly cost-effective compared to strategies using first-line drugs only. In our base case, standardized second-line treatment for confirmed MDR TB cases (STR2) had an incremental cost-effectiveness ratio of $720 per QALY ($8,700 per averted death) compared to DOTS. Individualized second-line drug treatment for MDR TB following first-line failure (ITR1) provided more benefit at an incremental cost of $990 per QALY ($12,000 per averted death) compared to STR2. A more aggressive version of the individualized treatment strategy (ITR2), in which both new and previously treated cases are tested for MDR TB, had an incremental cost-effectiveness ratio of $11,000 per QALY ($160,000 per averted death) compared to ITR1. The STR2 and ITR1 strategies remained cost-effective under a wide range of alternative assumptions about treatment costs, effectiveness, MDR TB prevalence, and transmission. CONCLUSIONS: Treatment of MDR TB using second-line drugs is highly cost-effective in Peru. In other settings, the attractiveness of strategies using second-line drugs will depend on TB incidence, MDR burden, and the available budget, but simulation results suggest that individualized regimens would be cost-effective in a wide range of situations

Worldwide Emergence of Extensively Drug-resistant Tuberculosis

Mycobacterium tuberculosis strains are becoming resistant to not only the most powerful first-line drugs but also many second-line drugs

High ethionamide resistance in Mycobacterium tuberculosis strains isolated in Kenya

Background: Increasing development of tuberculosis (TB) resistance to the currently available drugs including second-line anti-TB drugs that are being used for treatment of Multi-Drug Resistant TB (MDR-TB) patients has frustrated efforts to control TB worldwide. Ethionamide (Eth) is one of the drugs used in the regimen for treatment of these patients. Objective: To determine level of Ethionamide resistance among second-line anti-tuberculosis drugs in Mycobacterium tuberculosis (MTB) strains isolated in Kenya. Design: A retrospective lab-based study involving archived strains from previous studies carried out at the Centre for Respiratory Diseases Research (CRDR), Kenya Medical Research Institute (KEMRI) from 2002 to 2007. Setting: Centre for Respiratory Diseases Research (CRDR), Kenya Medical Research Institute (KEMRI). Methods: A total of 216 MTB strains with pre-determined first-line drug susceptibility testing (DST) results were used including 78 first-line resistant to individual and combined drugs, and 138 susceptible to streptomycin, rifampicin, isoniazid and ethambutol. The strains were subjected to DST to ethionamide among other second-line. Results: Thirty two [32/216 (14.8%)] strains showed resistance to second-line drugs. Resistance to Eth was the highest [18/32 (56.3%)] including co-resistance with isoniazid [8/18 (44.4%)]. Nine [9/18 (50%)] strains were fully resistant and 9 [9/18 (50%)] were intermediate resistant to Eth. Conclusion: Unexplainable high levels of Eth resistance is a cause for concern. This will impact negatively on the outcome of management of MDR-TB especially in Kenya where the use of this drug is almost mandatory. Close monitoring of Eth before initiating individual patient management may be necessary. Keywords: Ethionamide, Resistant, MDR-TB

Antibiotic control of antibiotic resistance in hospitals: a simulation study

<p>Abstract</p> <p>Background</p> <p>Using mathematical deterministic models of the epidemiology of hospital-acquired infections and antibiotic resistance, it has been shown that the rates of hospital-acquired bacterial infection and frequency of antibiotic infections can be reduced by (i) restricting the admission of patients colonized with resistant bacteria, (ii) increasing the rate of turnover of patients, (iii) reducing transmission by infection control measures, and (iv) the use of second-line drugs for which there is no resistance. In an effort to explore the generality and robustness of the predictions of these deterministic models to the real world of hospitals, where there is variation in all of the factors contributing to the incidence of infection, we developed and used a stochastic model of the epidemiology of hospital-acquired infections and resistance. In our analysis of the properties of this model we give particular consideration different regimes of using second-line drugs in this process.</p> <p>Methods</p> <p>We developed a simple model that describes the transmission of drug-sensitive and drug-resistant bacteria in a small hospital. Colonized patients may be treated with a standard drug, for which there is some resistance, and with a second-line drug, for which there is no resistance. We then ran deterministic and stochastic simulation programs, based on this model, to predict the effectiveness of various treatment strategies.</p> <p>Results</p> <p>The results of the analysis using our stochastic model support the predictions of the deterministic models; not only will the implementation of any of the above listed measures substantially reduce the incidences of hospital-acquired infections and the frequency of resistance, the effects of their implementation should be seen in months rather than the years or decades anticipated to control resistance in open communities. How effectively and how rapidly the application of second-line drugs will contribute to the decline in the frequency of resistance to the first-line drugs depends on how these drugs are administered. The earlier the switch to second-line drugs, the more effective this protocol will be. Switching to second-line drugs at random is more effective than switching after a defined period or only after there is direct evidence that the patient is colonized with bacteria resistant to the first antibiotic.</p> <p>Conclusions</p> <p>The incidence of hospital-acquired bacterial infections and frequencies of antibiotic resistant bacteria can be markedly and rapidly reduced by different readily implemented procedures. The efficacy using second line drugs to achieve these ends depends on the protocol used for their administration.</p